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Figure 1.
Intraocular pressure was measured by pneumatonometry. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .005; †P < .001). The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

Intraocular pressure was measured by pneumatonometry. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .005; †P < .001). The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

Figure 2.
A, Outflow facility was measured by fluorophotometry. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .03). Separately, all participants were pooled together and a Mann-Whitney test (B) or a linear regression analysis (C) was performed with outflow facility as the dependent variable. The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

A, Outflow facility was measured by fluorophotometry. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .03). Separately, all participants were pooled together and a Mann-Whitney test (B) or a linear regression analysis (C) was performed with outflow facility as the dependent variable. The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

Figure 3.
A, Uveoscleral outflow was determined by mathematical calculation. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .06; †P = .02). Separately, all participants were pooled together and a Mann-Whitney test (B), (‡P < .001) and a linear regression analysis (C) were performed with uveoscleral outflow as the dependent variable. The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

A, Uveoscleral outflow was determined by mathematical calculation. Comparisons between groups were made using Mann-Whitney tests with Bonferroni corrections for multiple comparisons (*P = .06; †P = .02). Separately, all participants were pooled together and a Mann-Whitney test (B), (‡P < .001) and a linear regression analysis (C) were performed with uveoscleral outflow as the dependent variable. The boxes are bound by the 25% and 75% quartiles; the lines through the boxes represent the median; the error bars end at the farthest data points that are not outliers; and the open circles indicate outliers (which are located at greater than 1.5 times the interquartile range either above or below the quartiles). OHT indicates ocular hypertension; ONT, ocular normotension; XFS, exfoliation syndrome.

Table. 
Comparison of Aqueous Humor Dynamics Among Patients With XFS With or Without OHT and Age-Matched Controls With or Without OHT
Comparison of Aqueous Humor Dynamics Among Patients With XFS With or Without OHT and Age-Matched Controls With or Without OHT
1.
Ritch  RSchlotzer-Schrehardt  U Exfoliation syndrome. Surv Ophthalmol 2001;45 (4) 265- 315
PubMedArticle
2.
Hammer  TSchlotzer-Schrehardt  UNaumann  GO Unilateral or asymmetric pseudoexfoliation syndrome? an ultrastructural study. Arch Ophthalmol 2001;119 (7) 1023- 1031
PubMedArticle
3.
Naumann  GOSchlotzer-Schrehardt  UKuchle  M Pseudoexfoliation syndrome for the comprehensive ophthalmologist: intraocular and systemic manifestations. Ophthalmology 1998;105 (6) 951- 968
PubMedArticle
4.
Ritch  RSchlotzer-Schrehardt  U Exfoliation (pseudoexfoliation) syndrome: toward a new understanding: proceedings of the First International Think Tank. Acta Ophthalmol Scand 2001;79 (2) 213- 217
PubMedArticle
5.
Aasved  H Relationship of intraocular pressure and fibrillopathia epitheliocapsularis. Trans Ophthalmol Soc U K 1979;99 (2) 310- 311
PubMed
6.
Mitchell  PWang  JJHourihan  F The relationship between glaucoma and pseudoexfoliation: the Blue Mountains Eye Study. Arch Ophthalmol 1999;117 (10) 1319- 1324
PubMedArticle
7.
Jeng  SMKarger  RAHodge  DOBurke  JPJohnson  DHGood  MS The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma 2007;16 (1) 117- 121
PubMedArticle
8.
Aasved  H The frequency of optic nerve damage and surgical treatment in chronic simple glaucoma and capsular glaucoma. Acta Ophthalmol (Copenh) 1971;49 (4) 589- 600
PubMedArticle
9.
Konstas  AGTsatsos  IKardasopoulos  ABufidis  TMaskaleris  G Preoperative features of patients with exfoliation glaucoma and primary open-angle glaucoma: The AHEPA study. Acta Ophthalmol Scand 1998;76 (2) 208- 212
PubMedArticle
10.
Konstas  AGStewart  WCStroman  GASine  CS Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 1997;28 (2) 111- 117
PubMed
11.
Lindblom  BThorburn  W Prevalence of visual field defects due to capsular and simple glaucoma in Halsingland, Sweden. Acta Ophthalmol (Copenh) 1982;60 (3) 353- 361
PubMedArticle
12.
Kozobolis  VPPapatzanaki  MVlachonikolis  IGPallikaris  IGTsambarlakis  IG Epidemiology of pseudoexfoliation in the island of Crete (Greece). Acta Ophthalmol Scand 1997;75 (6) 726- 729
PubMedArticle
13.
Kozart  DMYanoff  M Intraocular pressure status in 100 consecutive patients with exfoliation syndrome. Ophthalmology 1982;89 (3) 214- 218
PubMedArticle
14.
Ringvold  ABlika  SElsas  T  et al.  The middle-Norway eye-screening study, II: prevalence of simple and capsular glaucoma. Acta Ophthalmol (Copenh) 1991;69 (3) 273- 280
PubMedArticle
15.
Henry  JCKrupin  TSchmitt  M  et al.  Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure. Ophthalmology 1987;94 (5) 545- 552
PubMedArticle
16.
Klemetti  A Intraocular pressure in exfoliation syndrome. Acta Ophthalmol Suppl 1988;18454- 58
PubMed
17.
Puska  PVasara  KHarju  MSetala  K Corneal thickness and corneal endothelium in normotensive subjects with unilateral exfoliation syndrome. Graefes Arch Clin Exp Ophthalmol 2000;238 (8) 659- 663
PubMedArticle
18.
Ritch  RSchlotzer-Schrehardt  UKonstas  AG Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 2003;22 (3) 253- 275
PubMedArticle
19.
Ritch  R Exfoliation syndrome. Curr Opin Ophthalmol 2001;12 (2) 124- 130
PubMedArticle
20.
Schlötzer-Schrehardt  UNaumann  GO Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle glaucoma: a morphometric, ultrastructural study. Invest Ophthalmol Vis Sci 1995;36 (9) 1750- 1764
PubMed
21.
Gharagozloo  NZBaker  RHBrubaker  RF Aqueous dynamics in exfoliation syndrome. Am J Ophthalmol 1992;114 (4) 473- 478
PubMed
22.
Johnson  DHBrubaker  RF Dynamics of aqueous humor in the syndrome of exfoliation with glaucoma. Am J Ophthalmol 1982;93 (5) 629- 634
PubMed
23.
Stamper  RLLieberman  MFDrake  MV  Becker-Schaffer's Diagnosis and Therapy of the Glaucomas.  7th ed. St Louis, MO Mosby1999;101- 113
24.
Schenker  HIYablonski  MEPodos  SMLinder  L Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol 1981;99 (7) 1212- 1216
PubMedArticle
25.
Hayashi  MYablonski  MEMindel  JS Methods for assessing the effects of pharmacologic agents on aqueous humor dynamics. Tasman  WJaeger  EADuane's Foundations of Clinical Ophthalmology. Rev ed Philadelphia, PA Lippincott1993;1- 9
26.
Yablonski  MECook  DJGray  J A fluorophotometric study of the effect of argon laser trabeculoplasty on aqueous humor dynamics. Am J Ophthalmol 1985;99 (5) 579- 582
PubMed
27.
Toris  CBKoepsell  SAYablonski  MECamras  CB Aqueous humor dynamics in ocular hypertensive patients. J Glaucoma 2002;11 (3) 253- 258
PubMedArticle
28.
Yablonski  MEZimmerman  TJWaltman  SRBecker  B A fluorophotometric study of the effect of topical timolol on aqueous humor dynamics. Exp Eye Res 1978;27 (2) 135- 142
PubMedArticle
29.
Hayashi  MYablonski  MENovack  GD Trabecular outflow facility determined by fluorophotometry in human subjects. Exp Eye Res 1989;48 (5) 621- 625
PubMedArticle
30.
Toris  CBZhan  GFan  S  et al.  Effects of travoprost on aqueous humor dynamics in patients with elevated intraocular pressure. J Glaucoma 2007;16 (2) 189- 195
PubMedArticle
31.
Toris  CBCamras  CBYablonski  ME Acute versus chronic effects of brimonidine on aqueous humor dynamics in ocular hypertensive patients. Am J Ophthalmol 1999;128 (1) 8- 14
PubMedArticle
32.
Grant  WM Clinical measurements of aqueous flow. Arch Ophthalmol 1951;46113- 131Article
33.
Bleich  SRoedl  JVon Ahsen  N  et al.  Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol 2004;138 (1) 162- 164
PubMedArticle
34.
Schlötzer-Schrehardt  UZenkel  MKuchle  MSakai  LYNaumann  GO Role of transforming growth factor-beta 1 and its latent form binding protein in pseudoexfoliation syndrome. Exp Eye Res 2001;73 (6) 765- 780
PubMedArticle
35.
Määttä  MTervahartiala  THarju  MAiraksinen  JAutio-Harmainen  HSorsa  T Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma. J Glaucoma 2005;14 (1) 64- 69
PubMedArticle
36.
Schlötzer-Schrehardt  ULommatzsch  JKuchle  MKonstas  AGNaumann  GO Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2003;44 (3) 1117- 1125
PubMedArticle
37.
Nilsson  SF The uveoscleral outflow routes. Eye 1997;11 (pt 2) 149- 154
PubMedArticle
38.
Brubaker  RF Measurement of uveoscleral outflow in humans. J Glaucoma 2001;10 (5) ((suppl 1)) S45- S48
PubMedArticle
39.
Ocklind  A  Effect of latanoprost on the extracellular matrix of the ciliary muscle: a study on cultured cells and tissue sections. Exp Eye Res 1998;67 (2) 179- 191
PubMedArticle
40.
Sagara  TGaton  DDLindsey  JDGabelt  BTKaufman  PLWeinreb  RN Topical prostaglandin F2 alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway. Arch Ophthalmol 1999;117 (6) 794- 801
PubMedArticle
41.
Hepsen  IFOzkaya  E 24-h IOP control with latanoprost, travoprost, and bimatoprost in subjects with exfoliation syndrome and ocular hypertension. Eye 2007;21 (4) 453- 458
PubMed
42.
Konstas  AGHollo  GIrkec  M  et al.  Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer-masked, three-centre study. Br J Ophthalmol 2007;91 (6) 757- 760
PubMedArticle
43.
Konstas  AGKozobolis  VPKatsimpris  IE  et al.  Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma patients. Ophthalmology 2007;114 (4) 653- 657
PubMedArticle
44.
Konstas  AGMylopoulos  NKarabatsas  CH  et al.  Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. Eye 2004;18 (9) 893- 899
PubMedArticle
45.
Zabriskie  NNetland  PA Comparison of brimonidine/latanoprost and timolol/dorzolamide: two randomized, double-masked, parallel clinical trials. Adv Ther 2003;20 (2) 92- 100
PubMedArticle
46.
Bucci  MG Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma, Italian Latanoprost Study Group. J Glaucoma 1999;8 (1) 24- 30
PubMedArticle
47.
Bojić  LMandic  ZNovak-Laus  KSonicki  ZKarelovic  D A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma. Coll Antropol 2003;27 (2) 729- 734
PubMed
48.
Konstas  AGKozobolis  VPTersis  ILeech  JStewart  WC The efficacy and safety of the timolol/dorzolamide fixed combination vs latanoprost in exfoliation glaucoma. Eye 2003;17 (1) 41- 46
PubMedArticle
49.
Parmaksiz  SYuksel  NKarabas  VLOzkan  BDemirci  GCaglar  Y A comparison of travoprost, latanoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma. Eur J Ophthalmol 2006;16 (1) 73- 80
PubMed
50.
Davanger  MRingvold  ABlika  S The frequency distribution of the glaucoma tolerance limit. Acta Ophthalmol (Copenh) 1991;69 (6) 782- 785
PubMedArticle
51.
Puska  PVesti  ETomita  GIshida  KRaitta  C Optic disc changes in normotensive persons with unilateral exfoliation syndrome: a 3-year follow-up study. Graefes Arch Clin Exp Ophthalmol 1999;237 (6) 457- 462
PubMedArticle
52.
Konstas  AGKoliakos  GGKarabatsas  CH  et al.  Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humour of patients with exfoliative glaucoma. Exp Eye Res 2006;82 (2) 319- 322
PubMedArticle
53.
Gabelt  BTKaufman  PL Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res 2005;24 (5) 612- 637
PubMedArticle
54.
Tan  JCPeters  DMKaufman  PL Recent developments in understanding the pathophysiology of elevated intraocular pressure. Curr Opin Ophthalmol 2006;17 (2) 168- 174
PubMed
55.
Alvarado  JMurphy  CJuster  R Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology 1984;91 (6) 564- 579
PubMedArticle
56.
Rohen  JW Why is intraocular pressure elevated in chronic simple glaucoma? anatomical considerations. Ophthalmology 1983;90 (7) 758- 765
PubMedArticle
57.
Lütjen-Drecoll  EShimizu  TRohrbach  MRohen  JW Quantitative analysis of ‘plaque material' in the inner- and outer wall of Schlemm's canal in normal- and glaucomatous eyes. Exp Eye Res 1986;42 (5) 443- 455
PubMedArticle
58.
Selbach  JMPosielek  KSteuhl  KPKremmer  S Episcleral venous pressure in untreated primary open-angle and normal-tension glaucoma. Ophthalmologica 2005;219 (6) 357- 361
PubMedArticle
59.
Berson  FGEpstein  DL Separate and combined effects of timolol maleate and acetazolamide in open-angle glaucoma. Am J Ophthalmol 1981;92 (6) 788- 791
PubMed
60.
Kanno  MAraie  MKoibuchi  HMasuda  K Effects of topical nipradilol, a β blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans. Br J Ophthalmol 2000;84 (3) 293- 299
PubMedArticle
61.
Sponsel  WEMensah  JKiel  JW  et al.  Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye. Am J Ophthalmol 2000;130 (2) 151- 159
PubMedArticle
62.
Yablonski  MENovack  GDBurke  PJCook  DJHarmon  G The effect of levobunolol on aqueous humor dynamics. Exp Eye Res 1987;44 (1) 49- 54
PubMedArticle
63.
Blondeau  PTetrault  JPPapamarkakis  C Diurnal variation of episcleral venous pressure in healthy patients: a pilot study. J Glaucoma 2001;10 (1) 18- 24
PubMedArticle
64.
Brown  JDBrubaker  RF A study of the relation between intraocular pressure and aqueous humor flow in the pigment dispersion syndrome. Ophthalmology 1989;96 (10) 1468- 1470
PubMedArticle
65.
Camras  CBHaecker  NRZhan  GToris  CB Aqueous humor dynamics in patients with pigment dispersion syndrome [abstract]. Invest Ophthalmol Vis Sci 2003;442207
66.
Farrar  SMShields  MB Current concepts in pigmentary glaucoma. Surv Ophthalmol 1993;37 (4) 233- 252
PubMedArticle
67.
Ritch  R Pigment dispersion syndrome. Am J Ophthalmol 1998;126 (3) 442- 445
PubMedArticle
68.
Gottanka  JJohnson  DHGrehn  FLutjen-Drecoll  E Histologic findings in pigment dispersion syndrome and pigmentary glaucoma. J Glaucoma 2006;15 (2) 142- 151
PubMedArticle
69.
Takei  YMizuno  K Electron-microscopic study of pseudo-exfoliation of the lens capsule. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1978;205 (4) 213- 220
PubMedArticle
70.
Gabelt  BTGottanka  JLutjen-Drecoll  EKaufman  PL Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys. Invest Ophthalmol Vis Sci 2003;44 (5) 2118- 2125
PubMedArticle
Clinical Sciences
July 14, 2008

Aqueous Humor Dynamics in Exfoliation Syndrome

Author Affiliations

Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha.

Arch Ophthalmol. 2008;126(7):914-920. doi:10.1001/archopht.126.7.914
Abstract

Objective  To examine how aqueous humor dynamics are affected by exfoliation syndrome (XFS) with or without elevated intraocular pressure (IOP).

Methods  Eighty participants were divided into 4 groups: (1) those with XFS and ocular normotension (n = 25), (2) controls with ocular normotension without XFS, age-matched to group 1 (n = 25), (3) those with XFS and ocular hypertension (n = 15), and (4) controls with ocular hypertension without XFS, age-matched to group 3 (n = 15). Following washout of glaucoma medications, assessments were made of IOP, episcleral venous pressure, aqueous flow, outflow facility, and uveoscleral outflow. Differences were analyzed by group mean comparisons and linear regression analyses.

Results  Uveoscleral outflow was significantly decreased in individuals with XFS compared with age-matched controls and was independent of IOP. Patients with ocular hypertension (with or without XFS) exhibited decreased outflow facility compared with those with ocular normotension (with or without XFS). Aqueous flow was not affected by the level of IOP or the presence of XFS.

Conclusions  Exfoliation syndrome in normotensive and hypertensive eyes is associated with a decrease in uveoscleral outflow, whereas in hypertensive but not normotensive eyes, it is associated with reduced outflow facility.

Exfoliation syndrome (XFS) is an age-related disease of the extracellular matrix characterized by an accumulation of fibrillar exfoliation material on many ocular tissues.13 It is acknowledged by some as the most common identifiable cause of glaucoma.1,4 While data vary throughout the world, XFS has been said to account for 20% to 25% of open-angle glaucomas overall.1 The incidence of glaucoma in patients with XFS is as much as 10- to 15-fold higher than in the general population.57 Furthermore, the clinical prognosis for glaucoma is worse for patients with XFS. Compared with eyes with primary open-angle glaucoma, eyes with XFS generally have more severe optic disc and visual field damage on diagnosis, are less responsive to topical ocular hypotensive medication, and more often require surgical intervention.811

The association between XFS and glaucoma may result from the effect of XFS on intraocular pressure (IOP). The frequency of ocular hypertension (OHT) in patients with XFS has been reported to be 5 to 10 times higher than in the general population.1215 In patients with unilateral XFS, the affected eye has a higher IOP than the contralateral eye.8,16,17 The correlation between XFS and OHT has been attributed, at least partly, to deposition of exfoliative material by the epithelial cells of the trabecular meshwork and Schlemm's canal with subsequent degradation and obstruction of the tissues and pathway associated with conventional outflow.1820 The amount of exfoliative material deposited in and around the trabecular meshwork has been associated with increased IOP and the presence of glaucoma.20 Resistance to outflow via the conventional pathway is increased in eyes with XFS compared with healthy eyes,21 with the effect being significant in eyes with both XFS and OHT.22 Exfoliation syndrome, however, does not appear to be associated with a change in aqueous flow.21 The effect of XFS on uveoscleral (pressure-independent) outflow has not been investigated. We conducted this study to investigate the effects of XFS on aqueous humor dynamics in the presence or absence of OHT.

METHODS

This prospective, age-matched, controlled study enrolled 80 individuals. Patients were excluded if they had any of the following: history of chronic inflammatory eye disease; history of ocular trauma or infection within 6 months before enrollment; any abnormalities preventing reliable IOP or fluorophotometric readings; history of intraocular or ocular laser operations; history of hypersensitivity or intolerance to fluorescein, timolol, or acetazolamide; current use of any ophthalmic glucocorticoid; or history of ineffective IOP response to β-blockers or carbonic anhydrase inhibitors. This study was approved by the University of Nebraska Medical Center institutional review board. Informed consent was obtained from all participants before their enrollment in the study.

On the screening day, participants underwent a clinical ophthalmologic examination. Intraocular pressure was measured using pneumatonometry (Model 30 Classic; Reichert Ophthalmic Instruments, Depew, New York); IOPs were recorded as the mean of 3 consecutive measurements, alternating between eyes. An ophthalmologist performed a slitlamp examination and the presence of XFS was confirmed in at least 1 eye of all of the participants in the XFS group. Gonioscopy was performed and the mean of the superior, inferior, nasal, and temporal chamber angles was determined, with 0 being closed and 4 being wide open.23

Patients with a history of XFS and either OHT (n = 15) or ocular normotension (n = 25) comprised the 2 experimental groups. Healthy volunteers with ocular normotension (n = 25) and patients with OHT (n = 15) but no other remarkable ocular pathology were the 2 age-matched control groups. Following the screening examination, participants were divided into 4 groups: XFS with ocular normotension; ocular normotension without XFS; XFS with OHT; and ocular hypertension without XFS. Patients in the OHT groups had a clinical history of IOPs greater than 21 mm Hg and were found to have IOPs greater than 21 mm Hg on the screening day but may have had an IOP of 21 mm Hg or less thereafter. The OHT and ocular normotension control groups were age-matched to the XFS groups. Where applicable, the washout period of topical ocular drugs was 4 weeks for β-blockers and prostaglandin analogues, 2 weeks for α-2 agonists, and 5 days for carbonic anhydrase inhibitors.

Participants self-administered 6 drops of fluorescein solution, 2% (Alcon Laboratories, Ft Worth, Texas), topically into both eyes at 5-minute intervals beginning 6 to 10 hours before fluorophotometric scans were taken. Between 8:30 and 9:30 AM the following day, IOPs were measured. Anterior chamber depth was measured using an A-scan (PacScan 300AP Digital Biometric Ruler; SonoMed, Lake Success, New York) or a slitlamp-mounted pachymeter (Haag Streit, Mason, Ohio). The anterior chamber volume was calculated from the anterior chamber depth measurement.24 Central corneal thickness was measured using ultrasound (PacScan 300AP Digital Biometric Ruler, SonoMed) or slitlamp (Haag Streit) pachymetry. Episcleral venous pressure was measured by venomanometry (Eyetech LTD, Morton Grove, Illinois) as the mean of 3 consecutive measurements.

Fluorophotometry was performed using a scanning ocular fluorophotometer (FM-2 Fluorotron Master Ocular Fluorophotometer; OcuMetrics, Mountain View, California) as described previously.2530 Briefly, 4 sets of duplicate scans were collected at 45-minute intervals to determine the baseline aqueous flow rate. Participants were then given either 1 drop of timolol maleate, 0.5% (Bausch & Lomb Pharmaceuticals, Tampa, Florida), topically or 250 mg of acetazolamide (Diamox; Wyeth-Ayerst, Madison, New Jersey) by mouth. Beginning 1 hour later, 3 more fluorophotometric scans were taken at intervals of 45 minutes to determine 3 values for the drug-induced reduction of aqueous flow.25 Following each fluorophotometric scan, IOP was measured. These measurements were used to determine outflow facility, the ratio of change in aqueous flow to change in IOP.25,29 Fluorophotometric, rather than tonographic, measurements of outflow facility were used because fluorophotometry avoids pseudofacility and scleral rigidity, factors confounding tonography.31 Uveoscleral outflow was calculated mathematically as the difference between aqueous flow and trabecular outflow.27,30

Eyes from the patients with XFS were chosen to be included in the study (only 1 eye per patient) if they were the only eye to meet the study criteria (usually because of a history of cataract surgery in 1 eye and/or unilateral XFS [n = 31]); if they had greater severity of XFS (based on a higher IOP or more medications [n = 4]); or if they had longer history of XFS (n = 1). Random selection was used in patients with symmetrical XFS (n = 4). For age-matched controls in whom both eyes were eligible for participation, left or right eyes were selected to match the laterality of the corresponding XFS patient's study eye.

Group means were compared using Mann-Whitney tests with post hoc Bonferroni tests for multiple comparisons, where applicable. Univariate linear regression analyses were used to determine the effects of IOP on various parameters of aqueous humor dynamics when all participants were combined into a single data set. Multivariate linear regression analyses were used to determine if the effects of IOP on aqueous humor dynamics were related to the presence of XFS and vice versa, where XFS was treated as a binary variable. The multivariate linear regression analyses introduced an independent variable interaction term, which is statistically significant in cases in which 1 independent variable affects the dependent variable differently, depending on the value of a second independent variable. Values are reported as mean (SD).

RESULTS

Of the 80 participants enrolled in the study, 28 were male and 52 were female. Two controls were black and all others were white. The postmeasurement analysis used 17 right eyes and 23 left eyes in the XFS groups and 22 right eyes and 18 left eyes in the control groups.

The Table includes the IOPs of the XFS and control groups. Those with diagnosed XFS exhibited significantly higher IOPs than their control counterparts (P = .02). The Table and Figure 1 summarize the IOPs of the 4 subgroups. The 2 OHT groups had significantly higher IOPs than their corresponding ocular normotension groups (P < .001 for both comparisons). Additionally, the ocular normotension control group exhibited a significantly lower mean IOP than either XFS group (P = .005 compared with XFS and ocular normotension; P < .001 compared with XFS and OHT). The difference in IOP was not significant for the 2 OHT subgroups.

The episcleral venous pressure was similar in all groups (Table). When all participants in the study were pooled, the presence of XFS did not affect episcleral venous pressure, but a positive correlation existed between IOP and episcleral venous pressure (R2 = 0.13, P = .001). The multivariate linear regression model indicated that the correlation between IOP and episcleral venous pressure (R2 = 0.21, P = .005) was independent of the presence of XFS. The mean aqueous flow rates for each group ranged from 1.96 to 2.34 μL/min, were statistically similar in all groups (Table), and were not correlated with IOP or affected by the presence of XFS according to univariate and multivariate analyses.

The OHT group had a significantly lower mean outflow facility than the ocular normotension group (P = .03) (Table and Figure 2A). All other comparisons of outflow facility between and among groups were not different. The presence of XFS alone did not affect outflow facility (Figure 2B), but a univariate analysis revealed an inverse correlation between outflow facility and IOP that was highly significant (R2  = 0.31, P < .001) (Figure 2C). The relationship between IOP and outflow facility may be nonlinear (Figure 2C), an observation that has been noted previously.32 A similar inverse correlation between outflow facility and IOP was found in the multivariate analysis (R2 = 0.34, P < .001). Interestingly, the multivariate analysis also demonstrated an inverse relationship between outflow facility and the presence of XFS as well as an inverse relationship between outflow facility and the independent variable interaction term, both of which approached significance (P = .09 and P = .06, respectively). These results suggest that the presence of XFS might be associated with a reduced outflow facility and that the effects of XFS and IOP on outflow facility appear to be interdependent.

The combined XFS groups exhibited a significantly lower mean uveoscleral outflow compared with the combined OHT and ocular normotension group (P < .001) (Table and Figure 3B). Uveoscleral outflow was not different when comparing each of the 2 XFS groups with one another or the OHT and ocular normotension groups with one another (Table and Figure 3A). Uveoscleral outflow was lower in those with XFS and OHT compared with OHT alone (P = .02) and in those with XFS and ocular normotension compared with ocular normotension alone (P = .06) (Table and Figure 3A). The inverse relationship between uveoscleral outflow and the presence of XFS was independent of IOP according to a multivariate analysis (R2 = 0.21, P = .02), whereas IOP was not correlated with uveoscleral outflow.

Mean anterior chamber volume was 199 (40) μL in all participants with XFS (n = 40) and 169 (42) μL in all controls (n = 40). In the 4 groups, anterior chamber volume averaged 191 (40) μL in those with XFS and ocular normotension (n = 25), 166 (39) μL in those with ocular normotension (n = 25), 212 (38) μL in those with XFS and OHT (n = 15), and 174 (48) μL in those with OHT (n = 15).

Corneal thickness averaged 565 (43) μm in all participants with XFS (n = 40) and 536 (39) μm in all controls (n = 40). In the 4 groups, mean corneal thickness was 574 (48) μm in those with XFS and ocular normotension (n = 25), 548 (40) μm in those with ocular normotension (n = 25), 550 (26) μm in those with XFS and OHT (n = 15), and 516 (27) μm in those with OHT (n = 15).

COMMENT

This is the first study to demonstrate that uveoscleral outflow is reduced in XFS. It is a prospective study that includes appropriate age-matched controls. The uveoscleral outflow effect is independent of IOP and consistent with the pathophysiology of the condition. Exfoliation syndrome is associated with significantly upregulated homocysteine levels in the aqueous humor,33 upregulated transforming growth factor β1 expression in anterior segment tissues,34 and reduced matrix metalloproteinase activity.35,36 All of these factors impair the stability, organization, and integrity of the extracellular matrix. Because the extracellular matrix of the ciliary muscle appears to be an important factor influencing the rate of uveoscleral outflow,37 it is not surprising that a reduction in the outflow of aqueous humor through this pathway was found in XFS.

We used an indirect method for mathematically calculating uveoscleral outflow based on an expanded version of the Goldmann equation and experimental measurements of aqueous flow, outflow facility, IOP, and episcleral venous pressure.27,30 Currently, this is the only method to assess uveoscleral outflow in humans and it is not without its limitations.38 The calculation assumes that uveoscleral outflow is independent of IOP. Deviations from this assumption may cause errors in calculating uveoscleral outflow. Because uveoscleral outflow is so low in XFS, a difference in episcleral venous pressure as little as 1 mm Hg could change the calculated uveoscleral outflow value from a positive to a negative number. It is important to emphasize that each of the assumptions in the determination of uveoscleral outflow is made for all participants, and group mean differences reflect differential uveoscleral outflow rates associated with the various ocular conditions. Alternatively, negative uveoscleral outflow values may actually have a true physiological correlate in the form of reverse aqueous humor flow and/or fluorescein diffusion into the anterior chamber from the suprachoroidal space or the iris.

The mechanism of action for prostaglandin analogues, a widely prescribed class of topical ocular hypotensive medications, appears to partially increase uveoscleral outflow via remodeling of the extracellular matrix of the ciliary body.39,40 As such, prostaglandin analogues might be especially effective in patients with XFS. Indeed, patients with XFS seem to respond to prostaglandin analogues at least as well as patients with OHT or primary open-angle glaucoma,4143 though enhanced efficacy of these drugs in patients with XFS compared with patients without could be partially attributable to higher pretreatment IOPs, which are generally exhibited by patients with XFS. In patients with XFS, prostaglandin analogues demonstrate greater IOP control than β-blocker monotherapy44; prostaglandin analogue/α-2 agonist combination therapy is better than β-blocker/carbonic anhydrase inhibitor fixed combination therapy45; and prostaglandin analogue monotherapy is comparable with topical β-blocker/pilocarpine combination treatment46,47 and comparable with48 or only slightly less effective than β-blocker/carbonic anhydrase inhibitor combination therapy.49 While many of these comparisons also hold for patients with OHT and primary open-angle glaucoma, they demonstrate that prostaglandin therapy is effective at lowering IOP in XFS. However, it should be noted that even with a common IOP, patients with XFS might be at a greater risk for glaucomatous onset and progression than those without XFS.50 In a study that investigated cases of unilateral XFS with symmetrical IOPs, glaucomatous disc changes occurred only in the eyes with XFS.51 Thus, patients with XFS may require more aggressive ocular hypotensive treatment than patients with primary open-angle glaucoma to maintain a comparable rate of disease progression.

Interestingly, latanoprost has been shown to normalize the levels of various factors found to be at abnormal concentrations in the aqueous humor of XFS eyes, such as those involving the action of matrix metalloproteinases.52 This may indicate a further advantage beyond the mechanism of IOP reduction of treating XFS patients with prostaglandin analogues.

This study demonstrates that outflow facility tends to be lower in XFS when the condition is accompanied by OHT. This finding is consistent with the observations that increased resistance to outflow is found in eyes with XFS and very high IOPs compared with controls,22 but no such significant difference is found in eyes with unilateral XFS and normal pressures compared with the fellow eye.21 The causal nature of this association is undetermined. The outflow facility reduction in patients with XFS and OHT may be unrelated to their XFS and may be similar to the cause of OHT in patients without XFS.27 As such, an indirect association between XFS and outflow facility may exist and may be related to IOP as a confounding variable. Outflow facility is lower in eyes with OHT than in normotensive eyes27,53,54; the fact that OHT often occurs in eyes with XFS might account for the reduction in outflow facility that is often observed in conjunction with XFS.22 However, evidence opposed to this theory suggests that different mechanisms cause a reduction in outflow facility with or without XFS. Juxtacanicular plaque and trabecular cell loss, which may contribute to a decreased outflow facility in patients with glaucoma,55,56 have not been reported in XFS. However, exfoliative material in the trabecular meshwork has been discovered.18,20,57 As an alternative explanation, XFS may cause a reduction in outflow facility but only in a certain subset of patients with XFS who go on to develop OHT. Therefore, exfoliative material could contribute to impairment in conventional outflow, and, with increasing severity, would lead to OHT by reducing outflow facility.

Subtle, statistically insignificant trends in the current data might support this latter theory. Our study demonstrated a rather high level of variability in outflow facility measurements made in healthy controls (Figure 2A). It is possible that this reflects the fact that healthy controls with normal IOPs can sometimes have very high outflow facilities, even approaching 0.8 μL/min/mm Hg (Figure 2A). The other 3 groups in our study exhibited lower and more limited ranges of outflow facility values, possibly because each of the members of these other groups had at least 1 condition associated with impaired aqueous outflow, ie, OHT and/or XFS. Specifically, this difference between the 2 ocular normotension groups might reflect a tendency toward impairment in outflow facility that is associated with XFS but only becomes statistically significant as IOP rises. Alternatively, the difference in variability between groups may simply be due to measurement error and/or the presence of outliers. Fluorophotometric measurements of outflow facility are more difficult in patients with lower baseline IOPs, as aqueous flow suppressants tend to have a smaller effect on IOP.

We found no association between aqueous flow and either IOP or the presence of XFS. An association between IOP and episcleral venous pressure was found. This finding is similar to a recently published study,58 which found a positive correlation between IOP and episcleral venous pressure in patients with primary open-angle glaucoma and normal-tension glaucoma. We did not find any association between episcleral venous pressure and the presence of XFS. In this study, episcleral venous pressure was measured once at mid-morning before the administration of aqueous flow suppressors. Importantly, previous studies have demonstrated that neither topical β-blockers5962 nor carbonic anhydrase inhibitors59 significantly alter episcleral venous pressure and that episcleral venous pressure exhibits minimal diurnal variation.63 As such, our study's single episcleral venous pressure measurement was sufficient to accurately calculate conventional outflow and uveoscleral outflow rates.

Apparent similarities exist between the pathophysiology of pigment dispersion syndrome and XFS, ie, accumulation of abnormal material at the site of conventional drainage and reduction in outflow facility.22,64,65 Pigment dispersion syndrome is a known cause of glaucoma that has been linked to elevated IOPs.66,67 Studies of aqueous humor dynamics in patients with pigment dispersion syndrome report a reduction in outflow facility64,65 but no change in uveoscleral outflow.65 The etiology of this finding is likely due to an accumulation of pigment in the trabecular meshwork and a subsequent degradation of the conventional outflow pathway. Gottanka et al68 found that pigment granules within the trabecular meshwork cells of eyes with pigment dispersion syndrome were positively associated with decreased trabecular cell numbers, collapse of the intratrabecular spaces, and an increase in extracellular material in the meshwork, all of which probably contribute to impaired conventional outflow and development of OHT. The release of pigment in pigment dispersion syndrome does not appear to affect the uveoscleral pathway,65 which apparently is less susceptible to pigment accumulation.

In contrast to pigment dispersion syndrome, XFS might involve changes in the ciliary muscle and the surrounding extracellular matrix, including ciliary epithelial cell degeneration caused by exfoliative material–induced basement membrane destruction.69 Furthermore, XFS is a disorder of the extracellular matrix that results in increased matrix accumulation possibly due to alterations in matrix metalloproteinase concentrations.36 Uveoscleral outflow appears to be affected by the microarchitecture of the ciliary muscle extracellular matrix.70 Consistent with this observation, our study demonstrates that uveoscleral outflow is reduced in patients with XFS. Therefore, the mechanism of OHT in XFS appears to be different from that in pigment dispersion syndrome.

We demonstrate that XFS is associated with a reduction in aqueous outflow through the uveoscleral pathway. Patients with XFS and OHT also exhibit a decrease in outflow facility.22 Therefore, XFS patients with high IOPs are likely to demonstrate significant impairments in both aqueous humor outflow pathways. These findings of reduced uveoscleral outflow may explain the higher IOPs that are difficult to control, which in turn contribute to an enhanced risk of glaucomatous optic neuropathy. By targeting the specific changes in the eyes of patients with XFS, improved therapeutic modalities may be developed specifically for this condition.

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Article Information

Correspondence: Carol B. Toris, PhD, Department of Ophthalmology, 985840 Nebraska Medical Center, Omaha, NE 68198-5840 (ctoris@unmc.edu).

Submitted for Publication: September 7, 2007; final revision received December 14, 2007; accepted January 8, 2008.

Financial Disclosure: None reported.

Funding/Support: This study was supported by a summer student fellowship from Fight For Sight Inc, New York, New York (Mr Johnson) as well as an unrestricted grant from Research to Prevent Blindness Inc, New York. Dr Camras was a Research to Prevent Blindness senior scientific investigator.

Previous Presentations: This study was presented in part at the annual meeting of the American Glaucoma Society from March 2 to 5, 2006, Charleston, South Carolina; and the Association for Research in Vision and Ophthalmology from April 30 to May 4, 2006, Ft Lauderdale, Florida.

Additional Contributions: Anne Fitzpatrick, MD, Eyal Margalit, MD, and Richard Tamesis, MD, referred patients and Jane Meza, PhD, assisted with statistical analysis.

References
1.
Ritch  RSchlotzer-Schrehardt  U Exfoliation syndrome. Surv Ophthalmol 2001;45 (4) 265- 315
PubMedArticle
2.
Hammer  TSchlotzer-Schrehardt  UNaumann  GO Unilateral or asymmetric pseudoexfoliation syndrome? an ultrastructural study. Arch Ophthalmol 2001;119 (7) 1023- 1031
PubMedArticle
3.
Naumann  GOSchlotzer-Schrehardt  UKuchle  M Pseudoexfoliation syndrome for the comprehensive ophthalmologist: intraocular and systemic manifestations. Ophthalmology 1998;105 (6) 951- 968
PubMedArticle
4.
Ritch  RSchlotzer-Schrehardt  U Exfoliation (pseudoexfoliation) syndrome: toward a new understanding: proceedings of the First International Think Tank. Acta Ophthalmol Scand 2001;79 (2) 213- 217
PubMedArticle
5.
Aasved  H Relationship of intraocular pressure and fibrillopathia epitheliocapsularis. Trans Ophthalmol Soc U K 1979;99 (2) 310- 311
PubMed
6.
Mitchell  PWang  JJHourihan  F The relationship between glaucoma and pseudoexfoliation: the Blue Mountains Eye Study. Arch Ophthalmol 1999;117 (10) 1319- 1324
PubMedArticle
7.
Jeng  SMKarger  RAHodge  DOBurke  JPJohnson  DHGood  MS The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma 2007;16 (1) 117- 121
PubMedArticle
8.
Aasved  H The frequency of optic nerve damage and surgical treatment in chronic simple glaucoma and capsular glaucoma. Acta Ophthalmol (Copenh) 1971;49 (4) 589- 600
PubMedArticle
9.
Konstas  AGTsatsos  IKardasopoulos  ABufidis  TMaskaleris  G Preoperative features of patients with exfoliation glaucoma and primary open-angle glaucoma: The AHEPA study. Acta Ophthalmol Scand 1998;76 (2) 208- 212
PubMedArticle
10.
Konstas  AGStewart  WCStroman  GASine  CS Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 1997;28 (2) 111- 117
PubMed
11.
Lindblom  BThorburn  W Prevalence of visual field defects due to capsular and simple glaucoma in Halsingland, Sweden. Acta Ophthalmol (Copenh) 1982;60 (3) 353- 361
PubMedArticle
12.
Kozobolis  VPPapatzanaki  MVlachonikolis  IGPallikaris  IGTsambarlakis  IG Epidemiology of pseudoexfoliation in the island of Crete (Greece). Acta Ophthalmol Scand 1997;75 (6) 726- 729
PubMedArticle
13.
Kozart  DMYanoff  M Intraocular pressure status in 100 consecutive patients with exfoliation syndrome. Ophthalmology 1982;89 (3) 214- 218
PubMedArticle
14.
Ringvold  ABlika  SElsas  T  et al.  The middle-Norway eye-screening study, II: prevalence of simple and capsular glaucoma. Acta Ophthalmol (Copenh) 1991;69 (3) 273- 280
PubMedArticle
15.
Henry  JCKrupin  TSchmitt  M  et al.  Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure. Ophthalmology 1987;94 (5) 545- 552
PubMedArticle
16.
Klemetti  A Intraocular pressure in exfoliation syndrome. Acta Ophthalmol Suppl 1988;18454- 58
PubMed
17.
Puska  PVasara  KHarju  MSetala  K Corneal thickness and corneal endothelium in normotensive subjects with unilateral exfoliation syndrome. Graefes Arch Clin Exp Ophthalmol 2000;238 (8) 659- 663
PubMedArticle
18.
Ritch  RSchlotzer-Schrehardt  UKonstas  AG Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 2003;22 (3) 253- 275
PubMedArticle
19.
Ritch  R Exfoliation syndrome. Curr Opin Ophthalmol 2001;12 (2) 124- 130
PubMedArticle
20.
Schlötzer-Schrehardt  UNaumann  GO Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle glaucoma: a morphometric, ultrastructural study. Invest Ophthalmol Vis Sci 1995;36 (9) 1750- 1764
PubMed
21.
Gharagozloo  NZBaker  RHBrubaker  RF Aqueous dynamics in exfoliation syndrome. Am J Ophthalmol 1992;114 (4) 473- 478
PubMed
22.
Johnson  DHBrubaker  RF Dynamics of aqueous humor in the syndrome of exfoliation with glaucoma. Am J Ophthalmol 1982;93 (5) 629- 634
PubMed
23.
Stamper  RLLieberman  MFDrake  MV  Becker-Schaffer's Diagnosis and Therapy of the Glaucomas.  7th ed. St Louis, MO Mosby1999;101- 113
24.
Schenker  HIYablonski  MEPodos  SMLinder  L Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol 1981;99 (7) 1212- 1216
PubMedArticle
25.
Hayashi  MYablonski  MEMindel  JS Methods for assessing the effects of pharmacologic agents on aqueous humor dynamics. Tasman  WJaeger  EADuane's Foundations of Clinical Ophthalmology. Rev ed Philadelphia, PA Lippincott1993;1- 9
26.
Yablonski  MECook  DJGray  J A fluorophotometric study of the effect of argon laser trabeculoplasty on aqueous humor dynamics. Am J Ophthalmol 1985;99 (5) 579- 582
PubMed
27.
Toris  CBKoepsell  SAYablonski  MECamras  CB Aqueous humor dynamics in ocular hypertensive patients. J Glaucoma 2002;11 (3) 253- 258
PubMedArticle
28.
Yablonski  MEZimmerman  TJWaltman  SRBecker  B A fluorophotometric study of the effect of topical timolol on aqueous humor dynamics. Exp Eye Res 1978;27 (2) 135- 142
PubMedArticle
29.
Hayashi  MYablonski  MENovack  GD Trabecular outflow facility determined by fluorophotometry in human subjects. Exp Eye Res 1989;48 (5) 621- 625
PubMedArticle
30.
Toris  CBZhan  GFan  S  et al.  Effects of travoprost on aqueous humor dynamics in patients with elevated intraocular pressure. J Glaucoma 2007;16 (2) 189- 195
PubMedArticle
31.
Toris  CBCamras  CBYablonski  ME Acute versus chronic effects of brimonidine on aqueous humor dynamics in ocular hypertensive patients. Am J Ophthalmol 1999;128 (1) 8- 14
PubMedArticle
32.
Grant  WM Clinical measurements of aqueous flow. Arch Ophthalmol 1951;46113- 131Article
33.
Bleich  SRoedl  JVon Ahsen  N  et al.  Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol 2004;138 (1) 162- 164
PubMedArticle
34.
Schlötzer-Schrehardt  UZenkel  MKuchle  MSakai  LYNaumann  GO Role of transforming growth factor-beta 1 and its latent form binding protein in pseudoexfoliation syndrome. Exp Eye Res 2001;73 (6) 765- 780
PubMedArticle
35.
Määttä  MTervahartiala  THarju  MAiraksinen  JAutio-Harmainen  HSorsa  T Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma. J Glaucoma 2005;14 (1) 64- 69
PubMedArticle
36.
Schlötzer-Schrehardt  ULommatzsch  JKuchle  MKonstas  AGNaumann  GO Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2003;44 (3) 1117- 1125
PubMedArticle
37.
Nilsson  SF The uveoscleral outflow routes. Eye 1997;11 (pt 2) 149- 154
PubMedArticle
38.
Brubaker  RF Measurement of uveoscleral outflow in humans. J Glaucoma 2001;10 (5) ((suppl 1)) S45- S48
PubMedArticle
39.
Ocklind  A  Effect of latanoprost on the extracellular matrix of the ciliary muscle: a study on cultured cells and tissue sections. Exp Eye Res 1998;67 (2) 179- 191
PubMedArticle
40.
Sagara  TGaton  DDLindsey  JDGabelt  BTKaufman  PLWeinreb  RN Topical prostaglandin F2 alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway. Arch Ophthalmol 1999;117 (6) 794- 801
PubMedArticle
41.
Hepsen  IFOzkaya  E 24-h IOP control with latanoprost, travoprost, and bimatoprost in subjects with exfoliation syndrome and ocular hypertension. Eye 2007;21 (4) 453- 458
PubMed
42.
Konstas  AGHollo  GIrkec  M  et al.  Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer-masked, three-centre study. Br J Ophthalmol 2007;91 (6) 757- 760
PubMedArticle
43.
Konstas  AGKozobolis  VPKatsimpris  IE  et al.  Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma patients. Ophthalmology 2007;114 (4) 653- 657
PubMedArticle
44.
Konstas  AGMylopoulos  NKarabatsas  CH  et al.  Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. Eye 2004;18 (9) 893- 899
PubMedArticle
45.
Zabriskie  NNetland  PA Comparison of brimonidine/latanoprost and timolol/dorzolamide: two randomized, double-masked, parallel clinical trials. Adv Ther 2003;20 (2) 92- 100
PubMedArticle
46.
Bucci  MG Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma, Italian Latanoprost Study Group. J Glaucoma 1999;8 (1) 24- 30
PubMedArticle
47.
Bojić  LMandic  ZNovak-Laus  KSonicki  ZKarelovic  D A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma. Coll Antropol 2003;27 (2) 729- 734
PubMed
48.
Konstas  AGKozobolis  VPTersis  ILeech  JStewart  WC The efficacy and safety of the timolol/dorzolamide fixed combination vs latanoprost in exfoliation glaucoma. Eye 2003;17 (1) 41- 46
PubMedArticle
49.
Parmaksiz  SYuksel  NKarabas  VLOzkan  BDemirci  GCaglar  Y A comparison of travoprost, latanoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma. Eur J Ophthalmol 2006;16 (1) 73- 80
PubMed
50.
Davanger  MRingvold  ABlika  S The frequency distribution of the glaucoma tolerance limit. Acta Ophthalmol (Copenh) 1991;69 (6) 782- 785
PubMedArticle
51.
Puska  PVesti  ETomita  GIshida  KRaitta  C Optic disc changes in normotensive persons with unilateral exfoliation syndrome: a 3-year follow-up study. Graefes Arch Clin Exp Ophthalmol 1999;237 (6) 457- 462
PubMedArticle
52.
Konstas  AGKoliakos  GGKarabatsas  CH  et al.  Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humour of patients with exfoliative glaucoma. Exp Eye Res 2006;82 (2) 319- 322
PubMedArticle
53.
Gabelt  BTKaufman  PL Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res 2005;24 (5) 612- 637
PubMedArticle
54.
Tan  JCPeters  DMKaufman  PL Recent developments in understanding the pathophysiology of elevated intraocular pressure. Curr Opin Ophthalmol 2006;17 (2) 168- 174
PubMed
55.
Alvarado  JMurphy  CJuster  R Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology 1984;91 (6) 564- 579
PubMedArticle
56.
Rohen  JW Why is intraocular pressure elevated in chronic simple glaucoma? anatomical considerations. Ophthalmology 1983;90 (7) 758- 765
PubMedArticle
57.
Lütjen-Drecoll  EShimizu  TRohrbach  MRohen  JW Quantitative analysis of ‘plaque material' in the inner- and outer wall of Schlemm's canal in normal- and glaucomatous eyes. Exp Eye Res 1986;42 (5) 443- 455
PubMedArticle
58.
Selbach  JMPosielek  KSteuhl  KPKremmer  S Episcleral venous pressure in untreated primary open-angle and normal-tension glaucoma. Ophthalmologica 2005;219 (6) 357- 361
PubMedArticle
59.
Berson  FGEpstein  DL Separate and combined effects of timolol maleate and acetazolamide in open-angle glaucoma. Am J Ophthalmol 1981;92 (6) 788- 791
PubMed
60.
Kanno  MAraie  MKoibuchi  HMasuda  K Effects of topical nipradilol, a β blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans. Br J Ophthalmol 2000;84 (3) 293- 299
PubMedArticle
61.
Sponsel  WEMensah  JKiel  JW  et al.  Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye. Am J Ophthalmol 2000;130 (2) 151- 159
PubMedArticle
62.
Yablonski  MENovack  GDBurke  PJCook  DJHarmon  G The effect of levobunolol on aqueous humor dynamics. Exp Eye Res 1987;44 (1) 49- 54
PubMedArticle
63.
Blondeau  PTetrault  JPPapamarkakis  C Diurnal variation of episcleral venous pressure in healthy patients: a pilot study. J Glaucoma 2001;10 (1) 18- 24
PubMedArticle
64.
Brown  JDBrubaker  RF A study of the relation between intraocular pressure and aqueous humor flow in the pigment dispersion syndrome. Ophthalmology 1989;96 (10) 1468- 1470
PubMedArticle
65.
Camras  CBHaecker  NRZhan  GToris  CB Aqueous humor dynamics in patients with pigment dispersion syndrome [abstract]. Invest Ophthalmol Vis Sci 2003;442207
66.
Farrar  SMShields  MB Current concepts in pigmentary glaucoma. Surv Ophthalmol 1993;37 (4) 233- 252
PubMedArticle
67.
Ritch  R Pigment dispersion syndrome. Am J Ophthalmol 1998;126 (3) 442- 445
PubMedArticle
68.
Gottanka  JJohnson  DHGrehn  FLutjen-Drecoll  E Histologic findings in pigment dispersion syndrome and pigmentary glaucoma. J Glaucoma 2006;15 (2) 142- 151
PubMedArticle
69.
Takei  YMizuno  K Electron-microscopic study of pseudo-exfoliation of the lens capsule. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1978;205 (4) 213- 220
PubMedArticle
70.
Gabelt  BTGottanka  JLutjen-Drecoll  EKaufman  PL Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys. Invest Ophthalmol Vis Sci 2003;44 (5) 2118- 2125
PubMedArticle
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